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Biomedical subjects

H H Fudenberg

Publications and source records attributed to H H Fudenberg.

At least 127 records · Page 7Linked to original sources

Coexistence of multiple monoclonal immunoglobulins with identical constant regions in one patient.

Two populations of IgG molecules, designated F-IgG3(chi) and S-IgG3(chi), were isolated from a patient with multiple myeloma. The constant regions of the two molecules appear to be identical, since the heavy chains of both belong to the gamma 3 subclass and both molecules are positive for G3m(5), G3m(10), and G3m(11) but negative for G3m(21), Km(1) and Km(2) allotypes. In contrast, the two molecules have different variable regions, since (a) they do not share idiotypic determinant(s); (b) their light chains have different NH2 terminal amino acid sequences, and (c) both their heavy and light chains have different peptide maps and amino acid compositions. SDS-polyacrylamide gel electrophoresis showed that the F-IgG3(chi) molecules have two kinds of light chains. One, designated, chi n, has a normal molecular weight (approximately 23,000); the other, designated chi h, has a molecular weight of approximately 28,000.

Aged↗

Serological and biochemical analyses of M components in patients with transitional cell carcinoma of the urinary bladder.

Serological and biochemical studies were performed on M components isolated from 3 patients with transitional cell carcinoma of the urinary bladder (TCC). All were IgG1(K) proteins. 2 of the 3 belonged to the VKI subgroup, and these 2 also possessed cross-reactive idiotypic determinants. These findings are consistent with the ideas that M components in patients with a given kind of cancer may have restricted heterogeneity, and that the synthesis of an M component and the manifestation of a solid tumor may be related events in some patients who exhibit both abnormalities.

Amino Acid Sequence↗

Immunoglobulin allotypes and nonseminoma testicular cancer.

Gm, A2m, and Km allotypic markers were examined in 52 Dutch patients with nonseminoma testicular cancer. The distribution pattern of the immunoglobulin allotypes in different groups of patients, classified according to histological diagnosis, did not differ significantly from that in the normal population. These results indicate no relationship between nonseminoma testicular cancer and immunoglobulin allotypes.

Choriocarcinoma↗

Effects of 5,8-dideazaisofolic acid (IAHQ) on human tumor cells in culture and on normal and tumor-bearing hamsters.

The quinazoline analog of folic acid, 5,8-dideazaisofolic acid (IAHQ), was tested for its effects on the growth of human tumor cells in vitro and in vivo. Of 23 human tumor cell lines tested in vitro, 7 were inhibited by IAHQ (ED50, 5 X 10(-6) to 5 X 10(-7) M). For in vivo studies, human osteosarcoma (OS) cells from the IAHQ-sensitive line TE-85 were implanted intraperitoneally in newborn hamsters: in the group treated with IAHQ, only 30% of the animals developed OS, compared with 100% of those not treated with IAHQ. The effects of IAHQ injections on mitogenic responses and natural killer activity of lymphocytes from normal 3-month-old hamsters were also examined.

Animals↗

Immune response to connective tissue components of the basement membrane.

The immune response to connective tissue components of basement membrane (type IV collagen and laminin) and to interstitial collagen (type I) has been examined in human and murine systems. We also examined the role that immunologic sensitization to autologous connective tissue components might play in inducing an inflammatory response resulting in pathologic sequelae. Mice receiving a single subcutaneous injection of 5 micrograms type IV or type I murine collagens, or murine laminin in complete Freund's adjuvant mount a delayed-type hypersensitivity response characterized by a mononuclear cell infiltrate when challenged in the footpad with the sensitizing antigen. Cell-mediated immunity to these connective tissue antigens can be transferred to normal syngeneic mice with sensitized T-lymphocytes. In addition, repeated immunizations with these homologous connective tissue components elicit antibody responses in mice. Our data demonstrate the immunogenic nature of types IV and I collagen, and of laminin in a syngeneic murine model. We have demonstrated autoantibodies to the basement membrane and interstitial collagens in the sera of patients with scleroderma (systemic sclerosis); ELISA ratios correlate directly with the extent of pulmonary fibrosis in these patients. Anti-type IV collagen autoantibodies were found to be primarily IgM and anti-type I collagen antibodies, primarily IgG. An antibody response to autologous connective tissue antigens could lead to complement activation, immune complex formation, and deposition of the complexes along vascular endothelium with recruitment of blood monocytes in situ, mirroring the early scleroderma lesion (perivascular mononuclear cell filtrates). In vitro we examined the role of human peripheral blood mononuclear cells in the activation of fibroblasts. Adherent human blood monocytes release mediators which stimulate fibroblast proliferation and collagen deposition. A model is presented for the induction of immunity to autologous connective tissue components, leading to mononuclear cell inflammation, fibroblast activation and fibrosis. Selective immunity to basement membrane collagens may influence the clinical expression of diffuse connective tissue syndromes such as scleroderma (systemic sclerosis).

Animals↗

Bovine 'transfer factor': an oligoribonucleopeptide which initiates antigen-specific lymphocytes responsiveness.

Bovine transfer factor (TF)--active in initiating specific responsiveness in human thymus-derived (T) lymphocytes to purified protein derivative from Mycobacterium tuberculosis (PPD) in vitro--was partially purified from the dialyzable portion of medium from immune lymph node cells (DLNE). Its physiochemical properties and structure were determined by methods previously employed to characterize human PPD-specific TF isolated from dialyzable leukocyte extracts (DLE). Bovine TF had a molecular weight (MW) of 1100-3000, was destroyed by heating at 56 or 80 degrees C for 30 min, was soluble in water but not in phenol or ether, and could be precipitated with ethanol. Bovine TF activity eluted as a single peak after high-pressure reverse-phase liquid chromatography (HPLC); the active moiety contained at least one free co-planar cis-diol group, as shown by boronate affinity chromatography. Additional structural features were deduced by evaluating TF activity after incubation with various endonucleases, exonucleases, and peptidases, a phosphatase, and a protease. The combined results indicate that bovine TF specific for PPD is an oligoribonucleopeptide. A simplest case molecular model was constructed on the basis of the data obtained. A comparative evaluation of the physicochemical properties and structural features of bovine TF and human TF specific for PPD indicated striking similarities and some differences.

Animals↗

Autoimmunity to endometrium and ovary in endometriosis.

Antibody titres to whole ovary, theca cells, granulosa cells and endometrium were determined by passive haemagglutination and immunofluorescence assays in sera and in cervical and vaginal secretions from 13 patients with endometriosis. Antibody titres to endometrium (mean log2 +/- s.e.m., 7.08 +/- 0.80; P less than 0.0001), ovary (3.58 +/- 0.87; P = 0.0092), theca cells (4.42 +/- 0.73; P less than 0.0001) and granulosa cells (3.33 +/- 0.63; P = 0.0024) were significantly higher in the patients' sera than in sera from 15 normal non-pregnant females. Antibody titres to granulosa cells were elevated (7.97 +/- 1.46; P = 0.0424) in their cervical secretions. Antibody titres to all tissues tested were similar in vaginal secretions of patients and controls. Immunofluorescent antibody assay of biopsied endometrial tissue and sera from the patients revealed the antibodies to be primarily IgG and IgA. The results suggest that autoantibodies to endometrium and ovary are present in patients with endometriosis.

Adult↗

Neutrophil cytotoxicity for desialylated autologous human red cells in the presence of peanut agglutinin.

Normal human peripheral blood neutrophils have been shown to function as effector cells, exhibiting cytotoxic activity against allogeneic or desialylated autologous red cells and tumor cells in the presence of the plant lectins concanavalin A (ConA) and phytohemagglutinin (PHA). The present study demonstrates that human neutrophils are selectively cytotoxic against desialylated autologous erythrocytes in the presence of the plant lectin peanut agglutinin (PNA), which closely resembles the circulating anti-T agglutinin with specificity for exposed terminal beta D-galactosyl residues. Nondesialylated erythrocytes were resistant to lysis. This PNA-dependent neutrophil cytotoxicity (PNA-NC) was dependent on dose, time, temperature, and ratio of effector to target cells in a 4-hr 51Cr release assay. Optimum cytotoxicity (50-80%) was obtained within 4 hr with 20 micrograms/ml PNA and an erythrocyte:neutrophil ratio of 1:1 at 24 degrees C. The PNA-NC was completely abolished in the presence of 0.25 M galactose, the specific sugar substrate for PNA.

Arachis↗

Preferential synthesis of the G1m(1) allotype of IgG1 in the central nervous system of multiple sclerosis patients.

Quantitations of the G1m(1) and G1m(3) allotypic determinants of human immunoglobulin G were performed by radioimmunoassay on cerebrospinal fluid and serum samples from patients with multiple sclerosis and from patients with other neurological disorders. In multiple sclerosis patients that were heterozygous for these determinants, G1m(1) concentration in the cerebrospinal fluid was greatly increased-reflected by an increased ratio of G1m(1)-in comparison with that of patients with other neurological disorders. These results suggest that in the heterozygous multiple sclerosis patients, most of the plasma cells in the central nervous system that secrete oligoclonal immunoglobulin G preferentially synthesize G1m(1) IgG1 molecules.

B-Lymphocytes↗

Immunoglobulin E levels and antisperm antibody titers in infertile couples.

Immunoglobulin E (IgE) levels and antisperm antibody titers were determined in samples of serum and seminal plasma from 25 fertile men (Group A), 18 infertile men without measurable immunity to sperm (Group B), and 42 infertile men autoimmune to sperm (Group C), and in samples of serum and cervical and vaginal secretions from 25 fertile women (Group D), 28 infertile women without measurable immunity to sperm (Group E), and 32 infertile women isoimmune to sperm (Group F). Among the men, IgE levels in the serum, measured in international units per milliliter, were elevated in Group C (230 +/- 41, mean +/- SEM) as compared with Groups B (94 +/- 33, P less than 0.05) and A (55 +/- 8, P less than 0.001). In contrast, IgE levels in the seminal plasma in Group C (180 +/- 44) were not significantly different from those in Group B (48 +/- 21), but were higher than those in Group A (8 +/- 2, P less than 0.05). In the women, serum IgE levels were higher (P less than 0.001) in Group F, with isoimmunity to sperm (472 +/- 55), than in Groups E (219 +/- 32) and D (76 +/- 16). Wives of autoimmune husbands had somewhat, though not significantly, higher serum IgE levels (406 +/- 55), than had wives of nonautoimmune husbands (247 +/- 97). These results provide evidence for an elevated IgE response in subjects with significantly elevated antisperm antibody titers.

Antibodies↗

Polyclonal activation of human peripheral blood B lymphocytes by formaldehyde-fixed Salmonella paratyphi B. I. Immunoglobulin production without DNA synthesis.

A "new" polyclonal activator of human peripheral blood B cells, formaldehyde-fixed Salmonella paratyphi B, is described. This bacterium does not stimulate cell proliferation as measured by incorporation of tritiated thymidine but does stimulate a subpopulation of B cells to secrete large amounts of IgM, IgG, and IgA in 7-day cell cultures. The immunoglobulins (Ig) produced by cells responding to S. paratyphi B are not specific antibodies against the bacterial antigens. In comparison with other B cell activators (pokeweed mitogen, Staphylococcus aureus Cowan I, and lipopolysaccharide), S. paratyphi B stimulation produced greater amounts of IgM but less IgG than pokeweed mitogen (PWM) or S. aureus Cowan I; lipopolysaccharide failed to stimulate significant Ig production on day 7 in most cases. In addition, the response to S. paratyphi apparently did not require T cell collaboration. These results suggest that the B cell subpopulation(s) responding to S. paratyphi B may be more differentiated B cells than those responding to either PWM or S. aureus Cowan I. Peripheral blood mononuclear cells from five patients with common variable immunodeficiency without evidence of abnormal suppressor T cells or monocytes failed to respond to S. paratyphi B, whereas cells from two of the same patients responded well to S. aureus Cowan I and partially to PWM. Thus, S. paratyphi B appears to be superior to other B cell activators for studies of B cell function in normal and abnormal states.

B-Lymphocytes↗

Characterization of newly established human osteosarcoma cell line, LM-1.

The characteristics of Cell Line LM-1, established from a human osteosarcoma, have been studied extensively. The cell produced both bone-specific and placental-like alkaline phosphatases when treated with hydrocortisone 21-phosphate; they had specific membrane antigens tht reacted with sera from osteosarcoma patients. Injection of LM-1 cells into newborn hamsters treated with antilymphocyte serum produced nodular tumors. The characteristics of LM-1 suggest that this tumor cell line has unique features that may be useful in a variety of studies of human and animal osteosarcoma.

Alkaline Phosphatase↗

Mycobacterium fortuitum pulmonary infection associated with an antigen-selective defect in cellular immunity.

In this study we describe the first example of a well documented case of pulmonary infection caused by Mycobacterium fortuitum shown to be associated with an antigen-selective defect in cell-mediated immunity to this organism. Immunologic parameters were evaluated before, during and after antibiotic treatment with amikacin. A defect in cellular immunity to purified protein derivative from Myco. fortuitum, shown to be antigen-selective as indicated by normal responsiveness to purified protein derivative from Mycobacterium tuberculosis and several other common recall antigens, accompanied the prolonged infection by this organism. During the first three months of treatment with amikacin, the patient's clinical status improved coincident with the eradication of the organism from the sputum. During the next three months of therapy with amikacin, however, a generalized defect in cellular immunity developed, and the lung disease again progressed. The deteriorating clinical condition was presumably related to a generalized cellular immune anergy or hyporesponsiveness induced by the amikacin therapy. After three more months of treatment, the organism became resistant to the drug and reappeared in sputum cultures. Since amikacin therapy was discontinued, the patient's general immune responsiveness returned to normal. He did, however, remain unresponsive to purified protein derivative from Mycobacterium fortuitum.

Amikacin↗